Structural highlights
Disease
GLNA_HUMAN Defects in GLUL are the cause of congenital systemic glutamine deficiency (CSGD) [MIM:610015. CSGD is a rare developmental disorder with severe brain malformation resulting in multi-organ failure and neonatal death. Glutamine is largely absent from affected patients serum, urine and cerebrospinal fluid.[1]
Function
GLNA_HUMAN This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.[2]
Publication Abstract from PubMed
Glutamine synthetase (GS) is a decameric enzyme that plays a key role in nitrogen metabolism. Acetylation of the N-terminal degron (N-degron) of GS is essential for ubiquitylation and subsequent GS degradation. The full-length GS structure showed that the N-degron is buried inside the GS decamer and is inaccessible to the acetyltransferase. The structure of N-degron-truncated GS reported here reveals that the N-degron is not essential for GS decamer formation. It is also shown that the N-degron can be exposed to a solvent region through a series of conformational adjustments upon ligand binding. In summary, this study elucidated the dynamic movement of the N-degron and the possible effect of glutamine in enhancing the acetylation process.
Crystal structure of N-terminal degron-truncated human glutamine synthetase.,Chek MF, Kim SY, Mori T, Kojima H, Hakoshima T Acta Crystallogr F Struct Biol Commun. 2021 Nov 1;77(Pt 11):427-434. doi:, 10.1107/S2053230X21010748. Epub 2021 Oct 29. PMID:34726182[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Haberle J, Gorg B, Rutsch F, Schmidt E, Toutain A, Benoist JF, Gelot A, Suc AL, Hohne W, Schliess F, Haussinger D, Koch HG. Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med. 2005 Nov 3;353(18):1926-33. PMID:16267323 doi:353/18/1926
- ↑ Vermeulen T, Gorg B, Vogl T, Wolf M, Varga G, Toutain A, Paul R, Schliess F, Haussinger D, Haberle J. Glutamine synthetase is essential for proliferation of fetal skin fibroblasts. Arch Biochem Biophys. 2008 Oct 1;478(1):96-102. doi: 10.1016/j.abb.2008.07.009., Epub 2008 Jul 17. PMID:18662667 doi:10.1016/j.abb.2008.07.009
- ↑ Chek MF, Kim SY, Mori T, Kojima H, Hakoshima T. Crystal structure of N-terminal degron-truncated human glutamine synthetase. Acta Crystallogr F Struct Biol Commun. 2021 Nov 1;77(Pt 11):427-434. PMID:34726182 doi:10.1107/S2053230X21010748
